Molecular Docking Approach Reveals the Potential Role of Psidium Guajava Leaf Extract Compounds as Quorum-Sensing Inhibitors Targeting Pseudomonas Aeruginosa’s Lasr

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Molecular Docking Approach Reveals the Potential Role of Psidium Guajava Leaf Extract Compounds as Quorum-Sensing Inhibitors Targeting Pseudomonas Aeruginosa’s Lasr

1Ayu Tri Agustin, 2Ahdiah Imroatul Muflihah, 3Anas Fadli Wijaya, 4Hartalina Mufidah, 5Jepri Riranto
1,2,3,4Medical Laboratory Technology Study Program, Faculty of Health Sciences, Universitas dr. Soebandi, Indonesia, 68111
5Study Program of Nursing, Politeknik Yakpermas Banyumas, Indonesia, 53181
Orcid Id : 10000-0001-6742-2249


ABSTRACT:

Quorum-sensing LasR antagonism is evolving as a primary focus in promising new antivirulence approaches for treating bacterial infections. Pseudomonas aeruginosa’s LasR is a target receptor for developing alternative medicines in chronic wounds because it acts as an autoinducer in biofilm formation. Our research aims to predict the biofunction of Psidium guajava leaf water extract as an inhibitor of the quorum-sensing LasR of Pseudomonas aeruginosa. The 3D structures of five bioactive compounds (quercetin, gallocatechin, esculin, 3-sinapoylquinic acid, ellagic acid) and N-3-Oxo-Dodecanoyl-L-Homoserine Lactone (as positive control) were obtained from the PubChem Database. The Protein Data Bank database is used to download LasR. The active site of the LasR protein was determined using Molegro Virtual Docker 5.0. The docking simulation uses Molegro Virtual Docker 5.0 and Discovery Studio program version 21.1.1 for visualization. The results showed that the five compounds could bind to LasR at the active site and substrate binding, leading to the compound’s potential as an antibacterial for Pseudomonas aeruginosa by inhibiting the quorum-sensing receptor LasR. The 3-sinapoylquinic acid-LasR complex shows the lowest binding energy, namely -311.2 kJ/mol.

 

KEYWORDS:

anti-virulence, autoinducer, in silico, LasR, P. aeruginosa

 

REFERENCES :

1) Abid HMU, Hanif M, Mahmood K, Aziz M, Abbas G, Latif H (2022) Wound-Healing and Antibacterial Activity of the Quercetin–4-Formyl Phenyl Boronic Acid Complex against Bacterial Pathogens of Diabetic Foot Ulcer. ACS Omega 7: 24415–24422. https://doi.org/10.1021/acsomega.2c01819  
2) Agustin AT, Safitri A, Fatchiyah F (2020) An in Silico Approach Reveals the Potential Function of Cyanidin-3-o-glucoside of Red Rice in Inhibiting the Advanced Glycation End Products (AGES)-Receptor (RAGE) Signaling Pathway. Acta Inform. Medica 28: 170–179. https://doi.org/10.5455/aim.2020.28.170-179
3) Agustin AT, Julianto E, Julianus J, Riranto J (2022) Potential Role of Betel Leaf (Piper betle L.) Water Extract as Antibacterial Escherichia coli Through Inhibition of β-Ketoacyl-[Acyl Carrier Protein] Synthase I. Trop. J. Nat. Prod. Res. 6: 1802–1808. https://doi.org/10.26538/tjnpr/v6i11.10
4) Apridamayanti P, Meilinasary KA, Sari R (2016) Antibiotic Sensitivity in Pseudomonas aeruginosa of Diabetic Patient’s Foot Ulcer. Pharm. Sci. Res. 3: 80–87. https://doi.org/10.7454/psr.v3i2.3289
5) Bitencourt-Ferreira G, de Azevedo WFJ (2019) Molegro Virtual Docker for Docking. Methods Mol. Biol. 2053: 149–167. https://doi.org/10.1007/978-1-4939-9752-7_10
6) Bottomley MJ, Muraglia E, Bazzo R, Carfì A (2007) Molecular insights into quorum sensing in the human pathogen Pseudomonas aeruginosa from the structure of the virulence regulator LasR bound to its autoinducer. J. Biol. Chem. 282: 13592–13600. https://doi.org/10.1074/jbc.M700556200
7) Burgess JL, Wyant WA, Abdo Abujamra B, Kirsner RS, Jozic I (2021) Diabetic Wound-Healing Science. Medicina (B. Aires). 57: 1072. https://doi.org/10.3390/medicina57101072
8) Chin JD, Zhao L, Mayberry TG, Cowan BC, Wakefield MR, Fang Y (2023) Photodynamic Therapy, Probiotics, Acetic Acid, and Essential Oil in the Treatment of Chronic Wounds Infected with Pseudomonas aeruginosa. Pharmaceutics 15: 1721. https://doi.org/10.3390/pharmaceutics15061721
9) Ekom SE, Tamokou JDD (2018) Methanol Leaves Extract of Psidium guajava Linn. Exhibited Antibacterial and Wound Healing Activities. Int. J. Curr. Microbiol. Appl. Sci. 7: 4008–4023. https://doi.org/10.20546/ijcmas.2018.707.467
10) Ervita L, Hastuti L, Wuriani W (2022) Study Phenomenology Of Wound Care In Diabetic Foot Ulcer (DFU) Patients With Theory Of Planned Behavior Approach. Int. J. Progress. Sci. Technol. 34: 517. https://doi.org/10.52155/ijpsat.v34.2.4628
11) Gao D, Zhang Y, Bowers DT, Liu W, Ma M (2021) Functional hydrogels for diabetic wound management. APL Bioeng. 5: 31503. https://doi.org/10.1063/5.0046682
12) Gholami A, Minai-Tehrani D, Farewell A, Eriksson LA (2023) Discovery of novel inhibitors for Pseudomonas aeruginosa lipase enzyme from in silico and in vitro studies. J. Biomol. Struct. Dyn. 0: 1–14. https://doi.org/10.1080/07391102.2023.2203258
13) Heurlier K, Dénervaud V, Haenni M, Guy L, Krishnapillai V, Haas D (2005) Quorum-sensing- negative (lasR) mutants of Pseudomonas aeruginosa avoid cell lysis and death. J. Bacteriol. 187: 4875–83. https://doi.org/10.1128/JB.187.14.4875-4883.2005
14) Kiratisin P, Tucker KD, Passador L (2002) LasR, a Transcriptional Activator of Pseudomonas aeruginosa Virulence Genes, Functions as a Multimer. J. Bacteriol. 184: 4912–4919. https://doi.org/10.1128/JB.184.17.4912-4919.2002
15) Liu Y, Ahator S Dela, Wang H, Feng Q, Xu Y, Li C, Zhou X, Zhang L-H (2022) Microevolution of the mexT and lasR Reinforces the Bias of Quorum Sensing System in Laboratory Strains of Pseudomonas aeruginosa PAO1. Front. Microbiol. 13: 1–15. https://doi.org/10.3389/fmicb.2022.821895
16) Longo F, Rampioni G, Bondì R, Imperi F, Fimia GM, Visca P, Zennaro E, Leoni L (2013) A New
17) Transcriptional Repressor of the Pseudomonas aeruginosa Quorum Sensing Receptor Gene lasR. PLoS One 8: 1–9. https://doi.org/10.1371/journal.pone.0069554
18) McCready AR, Paczkowski JE, Henke BR, Bassler BL (2019) Structural determinants driving homoserine lactone ligand selection in the Pseudomonas aeruginosa LasR quorum-sensing receptor. Proc. Natl. Acad. Sci. U. S. A. 116: 245–254. https://doi.org/10.1073/pnas.1817239116
19) Purnamasari L, Victoria Carolino M, F. dela Cruz J (2022) The Antibacterial Properties of Psidium guajava Leaf Extract as a Wound Healing Agent of Laboratory Animals: a Review. Biotropika J. Trop. Biol.10:154–160. https://doi.org/10.21776/ub.biotropika.2022.010.02.10
20) Rancan, Contardi, Jurisch, Blume-Peytavi, Vogt, Bayer, Schaudinn (2019) Evaluation of Drug Delivery and Efficacy of Ciprofloxacin-Loaded Povidone Foils and Nanofiber Mats in a Wound-Infection Model Based on Ex Vivo Human Skin. Pharmaceutics 11: 527. https://doi.org/10.3390/pharmaceutics11100527
21) Sampath Kumar NS, Sarbon NM, Rana SS, Chintagunta AD, Prathibha S, Ingilala SK, Jeevan Kumar SP, Sai Anvesh B, Dirisala VR (2021) Extraction of bioactive compounds from Psidium guajava leaves and its utilization in preparation of jellies. AMB Express 11: 36. https://doi.org/10.1186/s13568-021-01194-9
22) Shahab M, Danial M, Khan T, Liang C, Duan X, Wang D, Gao H, Zheng G (2023) In Silico Identification of Lead Compounds for Pseudomonas Aeruginosa PqsA Enzyme: Computational Study to Block Biofilm Formation. Biomedicines 11: 961. https://doi.org/10.3390/biomedicines11030961
23) Srivastava P, Sivashanmugam K (2021) Efficacy of sub-MIC level of meropenem and ciprofloxacin against extensive drug-resistant (XDR) Pseudomonas aeruginosa isolates of diabetic foot ulcer patients. Infect. Genet. Evol. 92: 104824. https://doi.org/10.1016/j.meegid.2021.104824
24) Tribudi YA, Agustin AT, Setyaningtyas DE, Gusmalawati D (2022) Bioactive Compound Profile and Biological Modeling Reveals the Potential Role of Purified Methanolic Extract of Sweet
25) Flag (Acorus calamus L.) in Inhibiting the Dengue Virus (DENV) NS3 Protease-Helicase.
26) Indones. J. Chem. 22: 331–341. https://doi.org/10.22146/ijc.68317
27) Vestby LK, Grønseth T, Simm R, Nesse LL (2020) Bacterial Biofilm and its Role in the Pathogenesis of Disease. Antibiotics 9: 59. https://doi.org/10.3390/antibiotics9020059
28) Walicka M, Raczyńska M, Marcinkowska K, Lisicka I, Czaicki A, Wierzba W, Franek E (2021) Amputations of Lower Limb in Subjects with Diabetes Mellitus: Reasons and 30-Day Mortality. J. Diabetes Res. 2021: 1–8. https://doi.org/10.1155/2021/8866126

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